title: Inhibitory activity of salicylic acid on lipoxygenase-dependent lipid peroxidation.
abstract: BACKGROUND
  Since iron is essential for lipoxygenase activity and salicylic acid (SA) can interact with the metal, possible lipoxygenase inhibition by SA was investigated.
  
  
  METHODS
  Kinetic spectrophotometric evaluation of enzymatic lipid peroxidation catalyzed by soybean lipoxygenase (SLO), rabbit reticulocyte 15-lipoxygenase (RR15-LOX), porcine leukocyte 12-lipoxygenase (PL12-LOX) and human recombinant 5-lipoxygenase (HR5-LOX) with and without SA.
  
  
  RESULTS
  SA inhibited linoleic, arachidonic and docosahexaenoic acid or human lipoprotein peroxidation catalyzed by SLO with IC50 of, respectively, 107, 153, 47 and 108 microM. Using the same substrates, SA inhibited RR15-LOX with IC50 of, respectively, 49, 63, 27 and 51 microM. Further, arachidonic acid peroxidation catalyzed by PL12-LOX and HR5-LOX was inhibited by SA with IC50 of 101 and 168 microM, respectively. Enzymatic inhibition was complete, reversible and non-competitive. Conceivably due to its lower hydrophobicity, aspirin was less effective, indicating acetylation-independent enzyme inhibition. SA and aspirin were ineffective peroxyl radical scavengers but readily reduced Fe3+, i.e. FeCl3, to Fe2+, suggesting their capacity to reduce Fe3+ at the enzyme active site. Indeed, similar to the catecholic redox inhibitor nordihydroguaiaretic acid, SA inhibited with the same efficiency both ferric and the native ferrous SLO form, indicating that these compounds reduce the active ferric enzyme leading to its inactivation.
  
  
  CONCLUSIONS
  SA can inhibit lipoxygenase-catalyzed lipid peroxidation at therapeutic concentrations, suggesting its possible inhibitory activity against enzymatic lipid peroxidation in the clinical setting.
authors.affiliation: Dipartimento di Medicina e Scienze dell'Invecchiamento, and Centro di Scienze dell'Invecchiamento-Fondazione Università G. d'Annunzio, Facoltà di Medicina e Chirurgia, 66100 Chieti, Italy. dlapenna@unich.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Lapenna
authors.forename: Giuliano
authors.initials: G
authors.lastname: Ciofani
authors.forename: Sante Donato
authors.initials: SD
authors.lastname: Pierdomenico
authors.forename: Matteo
authors.initials: M
authors.lastname: Neri
authors.forename: Chiara
authors.initials: C
authors.lastname: Cuccurullo
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
authors.forename: Franco
authors.initials: F
authors.lastname: Cuccurullo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001092:Arachidonate 12-Lipoxygenase / Q000737:chemistry; D001093:Arachidonate 15-Lipoxygenase / Q000737:chemistry; D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry; D016718:Arachidonic Acid / Q000737:chemistry; D003864:Depression, Chemical; D004281:Docosahexaenoic Acids / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D006801:Humans; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation; D008084:Lipoxygenase / Q000737:chemistry*; D010084:Oxidation-Reduction; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry; D020156:Salicylic Acid / Q000737:chemistry*; D013025:Glycine max; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D011994:Recombinant Proteins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D008084:Lipoxygenase; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D020156:Salicylic Acid